Abstract Some studies indicate that breast cancer (BC) survivors are at significant risk for long- term cognitive deficits. Increasing BC survival rates may thus result in a large and rapidly growing cohort of women with extended disease-related disability. Adjuvant chemotherapy may be a significant contributing factor to cognitive impairments in BC. However, the role of chemotherapy in BC cognitive outcome is controversial. The specific cognitive deficits in BC, their incidence and underlying mechanisms are largely unknown due to a paucity of research in this area. There currently are no treatments for cognitive deficits related to BC. The goals of the proposed research are to 1) define the specific cognitive deficits associated with BC and chemotherapy using comprehensive, ecologically valid neuropsychological assessment, 2) elucidate the neurobiologic states underlying cognitive impairments in women with BC using advanced neuroimaging techniques, 3) identify demographic, medical and genetic factors associated with cognitive outcome in BC and 4) test the efficacy of two innovative treatment methods - one for improving existing cognitive impairments and the other for preventing cognitive impairments. The proposed research will implement highly innovative methods including measurement of hippocampal neural stem cells, using neurofeedback as a preventative treatment method and evaluating a combination of genetic variants believed to influence cognitive outcome. Results of this project will provide prognostic information regarding and treatment options for cognitive effects of BC, will address the lack of treatment methods for cognitive impairments in general by providing a new model of cognitive rehabilitation, and will increase our understanding of neural injury, recovery and repair. Additionally, cancer in general affects millions of individuals - males and females of all age groups, socioeconomic strata and ethnicities. Therefore, results from this project may have broad applications by providing direction for studies of cognitive effects in other cancers and conditions treated with chemotherapy.